Journal of Medical Genetics最新文献

{"title":"Short stature, brachydactyly and joint contractures associated with novel <i>FBN2</i> variants in two families.","authors":"Petra Loid, Fan Wang, Otto Lennartsson, Mari Muurinen, Alice Costantini, Sakshi Vats, Maria Lodefalk, Ola Nilsson, Outi Mäkitie","doi":"10.1136/jmg-2024-110533","DOIUrl":"https://doi.org/10.1136/jmg-2024-110533","url":null,"abstract":"<p><strong>Background: </strong>Fibrillinopathies comprise allelic disorders with opposing phenotypes. Pathogenic variants in fibrillin-2, encoded by <i>FBN2</i>, have mainly been associated with congenital contractural arachnodactyly but in a few cases also with brachydactyly.</p><p><strong>Methods and results: </strong>We recruited two families with index patients presenting with short stature (heights ≤3 SD scores), brachydactyly, joint contractures and facial dysmorphism as major features. In Family 2, the proband and father also had carpal tunnel syndrome. Radiographs showed signs of mild skeletal dysplasia with short long bones, brachydactyly and mild metaphyseal and vertebral irregularity. Whole genome sequencing revealed novel variants in the <i>FBN2</i> gene that segregated with the phenotype: in Family 1, a novel heterozygous missense variant c.4862G>A, p.(Cys1621Tyr) and in Family 2, a novel heterozygous deletion of exons 9-11. The missense variant affects a highly conserved residue and is predicted to be deleterious by most in silico tools. The <i>FBN2</i> deletion affects a well-conserved region and leads to loss of the transforming growth factor β binding-like 2 domain and part of the calcium-binding epidermal growth factor-like domain.</p><p><strong>Conclusion: </strong>Our findings suggest that short stature and mild skeletal dysplasia might be part of the spectrum of <i>FBN2-</i>related phenotypes. The study supports the role of <i>FBN2</i> variants in growth failure and expands the molecular spectrum of <i>FBN2</i> variants.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De novo heterozygous missense variants in <i>ATP11A</i> are associated with refractory focal epilepsy.","authors":"Zi-Long Ye, Nan-Xiang Shen, Xiang-Yun Luo, Hai-Sheng Lin, Yu-Tao Guo, Dong-Jie Qiu, Shi-Zhan Yuan, Ming-Feng He, Cui-Xia Fan, Wen-Bin Li, Yi-Wu Shi, Li-Bin Zhang","doi":"10.1136/jmg-2024-110540","DOIUrl":"https://doi.org/10.1136/jmg-2024-110540","url":null,"abstract":"<p><strong>Background: </strong><i>ATP11A</i> encodes an integral-membrane type IV P-type-adenosine triphosphatase that plays an important role in neural development by maintaining membrane lipid asymmetry. <i>ATP11A</i> de novo heterozygous missense variants have been reported to be associated with hypomyelinating leukodystrophy; however, the neurological symptoms of patients are often varying. In this study, we aimed to explore the relationship between <i>ATP11A</i> variants and epilepsy.</p><p><strong>Methods: </strong>Trio-based whole-exome sequencing was performed on patients with focal epilepsy. Multiple bioinformatics analyses were used to predict the pathogenicity of the variants. Previously reported literature was collected to analyse the relation between variants and phenotypes.</p><p><strong>Results: </strong>Two de novo heterozygous missense variants of <i>ATP11A</i> were identified in two unrelated patients with refractory focal epilepsy and were predicted to be pathogenic using multiple bioinformatics analyses. Then, six patients associated with missense variants were collected. Half of the patients (3/6) with variants located on/near the transmembrane regions (TMs) had more severe and multiple neurological symptoms, while the other half with non-TM variants had mild and single symptoms, indicating a correlation between variant location and phenotype. All patients showed progressively worsening conditions, potentially due to a gradually increased expression of <i>ATP11A</i> in the human brain over time.</p><p><strong>Conclusion: </strong>This study suggested that de novo heterozygous missense variants of <i>ATP11A</i> are associated with refractory focal epilepsy. Missense variant-associated phenotypes range from epileptic seizures to severe neurological symptoms. It should be noted that patients with <i>ATP11A</i> variants have a gradually worsening potential.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of genome sequencing in autism: illustrative examples from a genomic research study.","authors":"Thanuja Selvanayagam, Ny Hoang, Ege Sarikaya, Jennifer Howe, Carolyn Russell, Alana Iaboni, Morgan Quirbach, Christian R Marshall, Peter Szatmari, Evdokia Anagnostou, Jacob Vorstman, Dean M Hartley, Stephen W Scherer","doi":"10.1136/jmg-2024-110463","DOIUrl":"https://doi.org/10.1136/jmg-2024-110463","url":null,"abstract":"<p><strong>Background: </strong>Genetics is an important contributor to autism spectrum disorder (ASD). Clinical guidelines endorse genetic testing in the medical workup of ASD, particularly tests that use whole genome sequencing (WGS) technology. While the clinical utility of genetic testing in ASD is demonstrated, the breadth of impact of results can depend on the variant and/or gene being reported.</p><p><strong>Methods: </strong>We reviewed research results returned to families enrolled in our ASD WGS study between 2012 and 2023. For significant results, we grouped the outcome of each genetic finding into three outcome categories: (1) genetic diagnosis, (2) counselling benefits and (3) support to family.</p><p><strong>Results: </strong>Out of 202 families who received genome sequencing results, 100 had at least one clinically relevant finding related to ASD. With detailed examples, we show that all significant results led to a genetic diagnosis and counselling benefits.</p><p><strong>Conclusion: </strong>Our findings show the relevance of genome sequencing in ASD and provide illustrative examples of how the information can be used.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>AOPEP</i>-related autosomal recessive dystonia: update on Zech-Boesch syndrome.","authors":"Sylvia Boesch, Michael Zech","doi":"10.1136/jmg-2025-110656","DOIUrl":"https://doi.org/10.1136/jmg-2025-110656","url":null,"abstract":"<p><p>Gene discovery efforts have contributed to a better understanding of the molecular causes of dystonia, but knowledge of the individual monogenic forms remains limited. This review seeks to summarise all available data on the recently identified autosomal recessive subtype of dystonia caused by variants in <i>AOPEP</i>, focusing on the geographical origins of affected families, mutational spectrum, phenotypic expressions and pathophysiology. <i>AOPEP</i>-related dystonia, documented as Zech-Boesch syndrome in the Online Mendelian Inheritance in Man database, has been diagnosed in cohorts around the globe including under-represented populations with increased rates of consanguinity. Predictably leading to loss of protein function, the majority (74%) of disease-associated <i>AOPEP</i> alleles are protein-truncating variants comprising homozygous and compound heterozygous stop-gain, frameshift and splice-site changes. The dystonic disorder shows onset from childhood to the fourth decade and generalises in a significant proportion of cases (60%). Variable expressivity and age-related penetrance are likely to play a role in manifestation of the condition, consistent with occasional occurrence of <i>AOPEP</i> homozygous pathogenic variants in subjects without a diagnosis of dystonia. <i>AOPEP</i> encodes aminopeptidase O, a proteolytic processing enzyme that is preferentially expressed in glia and potentially linked to endosomal-lysosomal pathways. <i>AOPEP</i>-related autosomal recessive Zech-Boesch syndrome is of worldwide relevance for the diagnosis of genetic dystonia. Future research focusing on <i>AOPEP</i>`s role in cellular protein metabolism may provide new insights into dystonia pathogenesis and yet-unidentified therapeutic targets.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Very early-onset symptomatic CNS haemangioblastoma in Von Hippel-Lindau disease.","authors":"Marina Caballero, Vicente Santa-Maria Lopez, Laura Marti, Loreto Martorell, Diana Salinas, Jose Hinojosa, Maria Victoria Becerra, Miriam Pavon-Mengual, Andres Morales La Madrid, Ofelia Cruz, Jordi Muchart, Hector Salvador","doi":"10.1136/jmg-2024-110477","DOIUrl":"https://doi.org/10.1136/jmg-2024-110477","url":null,"abstract":"<p><p>Von Hippel-Lindau disease is a genetic disorder characterised by the development of a variety of tumours and cysts, with central nervous system (CNS) haemangioblastoma being the most common manifestation. Early diagnosis through genetic counselling and surveillance is crucial for detecting asymptomatic stages of the disease to minimise morbidity and mortality associated with tumour complications and treatment interventions. In this report, we describe two cases of very early-onset symptomatic CNS haemangioblastoma and discuss the potential improvement in surveillance protocols by including both clinical and genetic factors.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysing tumours for genetic diagnosis in mosaic neurofibromatosis type 1.","authors":"Tabea Isabelle Hartung, Lan Kluwe, Said Chosro Farschtschi","doi":"10.1136/jmg-2024-110580","DOIUrl":"https://doi.org/10.1136/jmg-2024-110580","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited disorder caused by pathogenic variants in the <i>NF1</i> gene, resulting in diverse clinical manifestations, especially multiple cutaneous neurofibromas. In approximately 50% of cases, variants occur de novo, and a portion of these cases involves genetic mosaicism, where variants are present in a subset of cells of an individual. Mosaic NF1 often presents with a milder phenotype and reduced transmission risk, complicating clinical diagnosis and genetic consulting. Conventional blood-based genetic testing may fail to detect the pathogenic variants in mosaic cases, necessitating additional analysis using tumour-derived DNA. We present five such cases and suggest a comprehensive diagnostic workflow focusing on tumour-based analysis for mosaic cases.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STIM1 in-frame deletion of eight amino acids in a patient with moderate tubular aggregate myopathy/Stormorken syndrome.","authors":"Emma Lafabrie, Maja Vrdoljak Pažur, Jocelyn Laporte, Johann Böhm","doi":"10.1136/jmg-2024-110273","DOIUrl":"https://doi.org/10.1136/jmg-2024-110273","url":null,"abstract":"<p><p>Store-operated Ca²⁺ entry (SOCE) is a ubiquitous mechanism controlling Ca²⁺ homeostasis and relies on the reticular Ca²⁺ sensor STIM1 and the plasma membrane Ca²⁺ channel ORAI1. <i>STIM1</i> and <i>ORAI1</i> gain-of-function mutations induce excessive Ca²⁺ influx through SOCE overactivation and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterised by muscle weakness and additional signs such as short stature, thrombocytopenia and hyposplenism. Most patients carry missense mutations in the STIM1 Ca²⁺-sensing EF-hands or in the CC1 domain implicated in ORAI1 activation.Here we report the first STIM1 deletion in a patient with moderate TAM/STRMK phenotype encompassing exercise-induced muscle weakness, elevated creatine kinase levels, asplenia and transient thrombocytopenia. The c.702_725del mutation occurred de novo and is predicted to involve the deletion of eight amino acids between EF-hands and the CC1 domain. We conducted a series of functional experiments in mouse and human cells lines and provided the evidence that the in-frame deletion causes constitutive STIM1 clustering and ORAI1 recruitment, resulting in profuse extracellular Ca²⁺ entry and major nuclear translocation of the transcription factor NFAT1. Overall, this work illustrated the pathogenicity of the STIM1 in-frame deletion at different levels of the SOCE pathway and provided a molecular diagnosis for the affected family.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the phenotypic spectrum of PROS: reclassifying isolated lateralised overgrowth.","authors":"Andrea Gazzin, Giuseppe Reynolds, Stefania Massuras, Maria Luca, Paola Coppo, Diana Carli, Marilidia Piglionica, Stefania Martino, Rosanna Bagnulo, Giovanni Battista Ferrero, Nicoletta Resta, Alessandro Mussa","doi":"10.1136/jmg-2024-110364","DOIUrl":"10.1136/jmg-2024-110364","url":null,"abstract":"<p><p>Lateralised overgrowth (LO) is characterised by the asymmetric increase in the size of any part of the body exceeding 10% compared with the unaffected contralateral one. LO is a key feature in various syndromic overgrowth disorders, such as Beckwith-Wiedemann spectrum and <i>PIK3CA</i>-related overgrowth spectrum (PROS). However, it can also present as isolated (ILO). Defining the aetiology of LO is critical due to the clinical implications and management strategies required for each condition. This report presents two patients who were followed up throughout childhood for ILO and were ultimately diagnosed with PROS through molecular analysis on DNA extracted from a skin biopsy, revealing the <i>PIK3CA</i>:c.263G>A (p.Arg88Gln) variant at a high variant allele frequency. This variant has been described in association with macrocephaly-capillary malformation syndrome but not with ILO. In conclusion, this is the first report of patients harbouring the (p.Arg88Gln) variant with a diagnosis of ILO, thus, highlighting the importance of considering ILO within the PROS and underscoring the necessity for somatic DNA testing. An early and accurate molecular diagnosis is crucial for guiding appropriate clinical management in order to ensure access to targeted therapies, emphasising the need for further research to refine diagnostic criteria and testing recommendations for ILO.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"276-280"},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arteriovenous malformation from a patient with JP-HHT harbours two second-hit somatic DNA alterations in <i>SMAD4</i>.","authors":"Evon DeBose-Scarlett, Andrew K Ressler, Cassi Friday, Kara K Prickett, James W Roberts, James R Gossage, Douglas A Marchuk","doi":"10.1136/jmg-2024-110569","DOIUrl":"10.1136/jmg-2024-110569","url":null,"abstract":"<p><strong>Background: </strong>Hereditary haemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations. It is caused by inherited loss-of-function mutations in one of three genes, <i>ENG</i>, <i>ACVRL1</i> or <i>SMAD4</i>. We recently showed that HHT-associated vascular malformations from liver, lung, brain and skin develop via a two-hit genetic mechanism resulting from biallelic loss-of-function mutations in either <i>ENG</i> or <i>ACVRL1</i>. Second-hit somatic mutations in <i>SMAD4</i> have not been reported in HHT-associated vascular malformations. Here, we investigate a large, aggressively growing craniofacial arteriovenous malformation (AVM) from an individual with juvenile polyposis-HHT caused by a germline mutation in <i>SMAD4</i>.</p><p><strong>Methods: </strong>We sequenced DNA from the AVM using a targeted gene sequencing panel to at least 1000X to identify somatic mutations that might contribute to the development of the AVM. We analysed whole genome SNP genotyping data using the algorithm Mosaic Chromosomal Alterations (MoChA) to identify somatic loss of heterozygosity.</p><p><strong>Results: </strong>We confirmed the germline mutation in <i>SMAD4</i> (c.1610A>T, p.Asp537Val) and identified a second-hit somatic mutation also in <i>SMAD4</i> (c.350dup, p.Tyr117*) that occurred in <i>trans</i> relative to the germline mutation. We also identified somatic loss of heterozygosity on the q arm of chromosome 18, including <i>SMAD4</i>. Additionally, we confirmed that the loss of heterozygosity causes loss of the wild-type allele. Thus, we identified two independent somatic alterations in <i>SMAD4</i> causing biallelic loss of <i>SMAD4</i> function in the AVM tissue.</p><p><strong>Conclusion: </strong>We identified biallelic loss of function of <i>SMAD4</i> in a craniofacial AVM, evidence that <i>SMAD4</i> also follows the two-hit mutation mechanism of HHT-associated vascular malformation pathogenesis.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"281-288"},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic features and pharmacological rescue of novel Kv7.2 variants in patients with epilepsy.","authors":"Yue Song, Yang Xia, Ziyue Peng, Yuhuan Meng, Wenwen Jing, Li Xie, Tianhua Cao, Jiahui Zhang, Huilin Song, Lingdi Meng, Yi Zhang, Shengbin Sui, Di Mao, Ying Jia, Shupei Qiao, Shihui Yu, Xue Zhang","doi":"10.1136/jmg-2024-110141","DOIUrl":"10.1136/jmg-2024-110141","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence indicates a robust correlation between epilepsy and variants of the Kv7.2 (<i>KCNQ2</i>) channel, which is critically involved in directing M-currents and regulating neuronal excitability within the nervous system. With the advancement of next-generation sequencing, the identification of <i>KCNQ2</i> variants has surged. Nonetheless, their functional impacts are still being determined, introducing uncertainty into the diagnostic process for affected families and potentially hindering their ability to participate in targeted precision medicine trials. This study aims to elucidate the pathogenicity of these novel variants and explore potential therapeutic interventions.</p><p><strong>Methods: </strong>Whole-cell patch-clamp recordings, western blotting, and immunofluorescent staining were performed to elucidate the functional consequences of the identified variants. Moreover, coimmunoprecipitation techniques were conducted to explore protein interactions, thus facilitating a deeper understanding of the underlying pathogenetic mechanisms contributing to the disease. Ultimately, the effects of pharmacological interventions were evaluated in vitro using the patch-clamp technique.</p><p><strong>Results: </strong>Herein, we identified 12 novel <i>KCNQ2</i> variants, further expanding the mutational spectrum of <i>KCNQ2</i>. Our investigation revealed that one gain-of-function variant (p.L102V (c.304C>G)) and three loss-of-function variants (p.H328Q (c.984C>G), p.A336V (c.1007C>T) and p.D563Efs*22 (c.1688_1689insACTT)) had different impacts on the binding of calmodulin and phosphati-dylinositol-4,5-bisphosphate, potentially altering their localisation and protein stability. Furthermore, the application of ML213, unlike Retigabine and ICA-069673, led to a significant increase in the current of p.H328Q.</p><p><strong>Conclusion: </strong>This study expanded the mutational spectrum of <i>KCNQ2</i> and analysed the genetic and functional consequences, as well as the pharmacological rescue, of four <i>de novo KCNQ2</i> variants. These findings offer valuable insights into the precise medicine of <i>KCNQ2</i>-related epilepsy.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"231-241"},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}